Ascorbic acid (vitamin C) is an antioxidant which is widely employed in cosmetics. Together with vitamin E it counteracts the oxidation of unsaturated fatty acids and thus also prevents lipoperoxide formation O. Isler, G. Brubacher, S. Ghisla, B. Krxc3xa4utler eds.; Vitamine II (vitamins II), G. Thieme Verlag, Stuttgart, N.Y., 431, 1988). As a vitamin, ascorbic acid is also involved in the metabolism, for instance in the hydroxylation of proline in collagen synthesis (J. J. Burns, J. M. Rivers, L. J. Machin eds.; Third Conference on vitamin C, Ann. N. Y. Acad. Sci., 498 (1987) 1-533).
On account of the excessively low stability of ascorbic acid in cosmetic formulations, it is often necessary to employ stabilized derivatives of ascorbic acid. Examples of these are sodium L-ascorbate monophosphate (JP 07082127, JP 05331020), L-ascorbic acid 2-O-D-glucoside (T. Sakamoto et al.; 19th IFSCC Congress, Sydney, 1996, Vol. 2, Paper No. 14) and 5,6-isopropylidene-L-ascorbic acid 2-phosphate (JP 08269074).
The abovementioned stabilized ascorbic acid derivatives, however, frequently have the disadvantage that they are too poorly soluble in cosmetic or pharmaceutical oils.
It is therefore an object of the invention to make available stable ascorbic acid derivatives, which do not have the abovementioned disadvantages, for cosmetic and pharmaceutical preparations.
We have found that this object is achieved according to the invention by use of ascorbic acid derivatives of the formula I, 
where the variables independently of one another have the following meanings:
R1 is hydrogen, C1-C20-acyl, C1-C12-alkoxycarbonyl, C1-C12-alkyl;
R2 is hydrogen, C1-C20-acyl, C1-C12-alkoxycarbonyl, C1-C12-alkyl,
where R1 and R2, together with the oxygen atoms to which they are bonded and the carbon atoms bonded to the oxygen atoms, can form an unsubstituted or substituted heterocycle;
R3 is hydrogen or a cation selected from the group consisting of NH4+, alkali metal and alkaline earth metal cations;
R4 is C1-C12-alkoxycarbonyl,
for cosmetic and pharmaceutical preparations.
Preferred compounds of formula I are those where the variables have the following meanings:
R1 is hydrogen, C1-C20-acyl, C1-C12-alkoxycarbonyl, C1-C12-alkyl;
R2 is hydrogen, C1-C20-acyl, C1-C12-alkoxycarbonyl, C1-C12-alkyl,
where R1 and R2, together with the oxygen atoms to which they are bonded and the carbon atoms bonded to the oxygen atoms, can form an unsubstituted or substituted heterocycle, and
R1 must not be a C1-C12-alkoxycarbonyl radical if R2 is hydrogen;
R3 is hydrogen or a cation selected from the group consisting of NH4+, alkali metal and alkaline earth metal cations;
R4 is C1-C12-alkoxycarbonyl.
Very particularly preferred compounds of the formula I are those where the variables have the following meanings:
R1 is hydrogen, C1-C20-acyl, C1-C6-alkoxycarbonyl;
R2 is hydrogen, C1-C20-acyl, C1-C6-alkoxycarbonyl,
where R1 must not be a C1-C6-alkoxycarbonyl radical if R2 is hydrogen;
R3 is hydrogen or a cation selected from the group consisting of NH4+, alkali metal and alkaline earth metal cations;
R4 is C1-C6-alkoxycarbonyl.
In the ascorbic acid derivatives of the formula I according to the invention, acyl radicals for R1 and R2 are to be understood as meaning branched or unbranched, saturated or unsaturated, if appropriate polyunsaturated, C1-C20-acyl chains.
Examples of these are acyl radicals of formic, acetic, propionic, n-butyric, isobutyric, sorbic, n-valeric, isovaleric, caproic, caprylic, capric, undecanoic, lauric, tridecanoic, myristic, pentadecanoic, palmitic, palmitoleic, stearic, oleic, linoleic, linolenic, nonadecanoic and arachidonic acid.
Preferred acyl radicals are those of long-chain fatty acids having C10 to C20 carbon chains, in particular acyl radicals of lauric, palmitic, palmitoleic, stearic, oleic and linoleic acid.
Alkyl radicals R1 and R2 which may be mentioned are branched or unbranched C1-C12-alkyl chains, preferably methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl.
Particularly preferred alkyl radicals are Cl-C6-alkyl chains, in particular methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl.
The radicals R1 and R2, together with the oxygen atoms to which they are bonded and the carbon atoms bonded to the oxygen atoms, can form unsubstituted or substituted heterocycles. These are intended to include, for example, cyclic acetals and ketals which, inter alia, are employed as a protective group for the two terminal hydroxyl functions (in the 5- and 6-position) of the acorbic acid. A preferred heterocyclic system is, inter alia, the 5,6-isopropylidene radical, which is formed by reaction of the two free hydroxyl groups in the 5- and 6-position with acetone.
Suitable alkoxycarbonyl radicals for R1, R2 and R4 are those whose alkoxy group contains 1 to 12 C atoms, preferably 1 to 6 C atoms, particularly preferably 1 to 4 C atoms.
Examples of the preferred radicals which may be mentioned are:
methoxycarbonyl
isopropoxycarbonyl
1-methylpropoxycarbonyl
n-pentoxycarbonyl
3-methylbutoxycarbonyl
2,2-dimethylpropoxycarbonyl
1-methyl-1-ethylpropoxycarbonyl
ethoxycarbonyl
n-propoxycarbonyl
n-butoxycarbonyl
2-methylpropoxycarbonyl
1,1-dimethylpropoxycarbonyl
hexoxycarbonyl
Particularly preferred alkoxycarbonyl radicals are:
methoxycarbonyl
isopropoxycarbonyl
1-methylpropoxycarbonyl
ethoxycarbonyl
n-propoxycarbonyl
n-butoxycarbonyl
Possible cations for R3 are NH4+ and representatives from the group consisting of the alkali and alkaline earth metals, preferably Na, K, Li, Ca and Mg, particularly preferably Na, K and Mg.
The term ascorbic acid derivatives is understood as meaning both derivatives of L- and D-ascorbic acid (isoascorbic acid), preferably L-ascorbic acid.
Some di- and tricarbonates of ascorbic acid are already known. Thus U.S. Pat. No. 2,980,702 describes compounds of the 2,5,6-tri-O-(C1-C3-alkoxycarbonyl)-L-ascorbic acid type and their use as a heat-resistant additive in foodstuffs, especially in baked goods.
JP 42020050 describes the synthesis of 2,6-di-O-(C1-C3-alkoxy-carbonyl)-L-ascorbic acid as a heat-stable derivative of ascorbic acid.
The use of the abovementioned ascorbic acid derivatives in cosmetic and pharmaceutical applications, however, is novel.
The stable ascorbic acid derivatives of the formula I according to the invention are outstandingly suitable as active compounds for cosmetic and pharmaceutical preparations.
Thus the compounds are distinguished, inter alia, in that, by variation of the radicals R1, R2 and R4, the lipophilicity of the ascorbic acid derivatives can be adjusted in a controlled manner. Depending on the demand in the formulation of cosmetic and pharmaceutical preparations, a wide range of stable vitamin C derivatives is thus available to the expert in the field. The tricabonates and the fatty acid esters of vitamin C 2-mono-carbonate particularly can be incorporated very readily into preparations such as, for example, ointments, lotions, gels or emulsions on account of their good oil solubility.
Accordingly, the present invention also relates to cosmetic and pharmaceutical preparations comprising an effective amount of at least one of the compounds of the formula I, and customary cosmetic and pharmaceutical auxiliaries and additives.
The abovementioned preparations can contain the compounds of the formula I in proportions of from 0.01 to 10% by weight, preferably 0.1 to 8% by weight, particularly preferably 0.5 to 5% by weight, based on the total amount of the cosmetic or pharmaceutical preparation.
The ascorbic acid derivatives of the formula I can be employed, inter alia, in all cosmetic and pharmaceutical preparations which, in addition to water, also contain emulsifiers, stabilizers, natural oils, cosmetic oils, fats, waxes, silicone oils, silicone oil derivatives, solubilizers, sunscreens, moisturizers, active compounds, consistency-imparting agents, gel-forming agents, antioxidants or preservatives.
Emulsifiers used are, for example, the following substances:
Polyglycerol fatty acid esters, ethoxylates of fatty acids, sorbitan fatty acid esters, phosphoric acid esters of fatty acids, phospholipids, glycerol monostearate and self-emulsifying glycerol monostearate.
Stabilizers are understood as meaning:
Magnesium and aluminum salts of fatty acids, complexing agents such as EDTA, NTA, MGDA, antioxidants such as BHT, BHA, alpha tocopherol, gallic acid and its salts and esters.
Natural oils are, for example, jojoba oil, sunflower oil, groundnut oil, almond oil, avocado oil, macadamia nut oil, castor oil, maize germ oil, grapeseed oil.
Cosmetic oils are, for example, isopropyl esters of fatty acids, very particularly isopropyl stearate, isopropyl palmitate, isopropyl isostearate, isopropyl myristate, isopropyl laurate, paraffin oil, neutral oil.
Cosmetic active compounds are, for example, panthenol, bisabolol, xcex1-tocopherol, xcex1-tocopheryl acetate, Aloe vera, algal extract, hyaluronic acid, retinol and retinyl esters, phytantriol, panthenyl ethyl ether, ferulic acid.
Sunscreens which can be used on their own or as a mixture together with the compounds of the formula I are, for example
The ascorbic acid derivatives of the formula I are also suitable for surfactant formulations.
Thus hair rinses, shampoos, and foams with stable vitamin C of the formula I can be prepared without problems.
The combination of anionic and cationic surfactants does not restrict use in cosmetic products.
The invention furthermore relates to ascorbic acid derivatives of the formula Ia, 
where the variables independently of one another have the following meanings:
R1 and R2 independently of one another are hydrogen or C1-C20-acyl;
R3 is hydrogen or a cation selected from the group consisting of alkali metals and alkaline earth metals;
R4 is C1-C6-alkoxycarbonyl.
Also claimed are ascorbic acid derivatives of the formula Ib, 
where
R3 is hydrogen or a cation selected from the group consisting of alkali metals and alkaline earth metals, and
R4 is C1-C6-alkoxycarbonyl.
Acyl radicals for R1 and R2 are understood as meaning branched or unbranched, saturated or unsaturated, if appropriate polyunsaturated, C1-C20-acyl chains.
Examples of these are acyl radicals of the formic, acetic, propionic, n-butyric, isobutyric, n-valeric, isovaleric, caproic, caprylic, capric, undecanoic, lauric, tridecanoic, myristic, pentadecanoic, palmitic, palmitoleic, stearic, oleic, linoleic, linolenic, nonadecanoic and arachidonic acid.
Preferred acyl radicals are those of long-chain fatty acids having C10 to C20 carbon chains, in particular acyl radicals of lauric, palmitic, palmitoleic, stearic, oleic and linoleic acid.
Suitable alkoxycarbonyl radicals for R4 are those whose alkoxy group contains from 1 to 6 C atoms, particularly preferably 1 to 4 C atoms.
Particularly preferred alkoxycarbonyl radicals are:
methoxycarbonyl
isopropoxycarbonyl
1-methylpropoxycarbonyl
ethoxycarbonyl
n-propoxycarbonyl
n-butoxycarbonyl
Possible cations for R3 are representatives of the group consisting of the alkali metals and alkaline earth metals, preferably Na, K, Li, Ca and Mg, particularly preferably Na, K and Mg.
The synthesis of the ascorbic acid derivatives of the formulae Ia and Ib, starting from the starting materials IIa and IIb, is carried out analogously to the process according to Japanese Patent Publication JP 42020050. Reference is made to this publication with respect to closer details.
In the following examples, the preparation of the ascorbic acid derivatives of the formula I according to the invention and the composition of cosmetic formulations which contain these ascorbic acid derivatives is illustrated in greater detail.